It has been well established that the immune system possesses strong tumor surveillance mechanisms and anti-tumor responses. Treatments utilizing engineered T cells have the potential to offer long-term protection, through memory, but it is unclear which T cell subset should be used. Our lab focuses on modulating invariant natural killer T (NKT) cells for cancer immunotherapy. NKT cell-based therapy offers the possibility of inducing an initial cytotoxic tumor response, in addition to activating NK cells and the adaptive immune system to produce tumor-directed cytotoxic T cells with long-lived memory. Thus NKT cells can mediate direct anti-tumor effects and also activate other immune pathways. We hypothesize that transducing NKT cells with anti- CD19 chimeric antigen receptors (CAR) will enhance their cytotoxic functions and will be more efficient than transducing bulk T cells. In order to test this hypothesis we will transduce NKT cells and bulk T isolated from the peripheral blood of healthy donors and lymphoma patients. We will characterize our CAR expressing NKT/T cells by assessing their phenotype, proliferative capacity, and function. We will compare their anti-tumor effector functions utilizing in vitro T cell assays and cytotoxicity studies, as wll as using mouse xenograft models. The information gained in these studies will serve to help understand and design NKT cell based immunotherapeutic approaches for the treatment of cancer.